Sythesis of polypeptide models of collagen. The synthesis of several sequential oligomer models of collagen is reported. Polytripeptides H(-Pro-Gly-Leu)n OH, H(-Pro-Gly-Phe)n OH, H(-Pro-Sar-Gly)n OH, H-(Sar-Pro-Gly-)n -OH, H(-Pro-Gly-V-AL-)N OH and H(-Gly-Val-Pro)n -oh were synthesized by the active ester method. Preliminary fractionation and mol.wt. determination showed typical gaussian distributions. Good yields were obtained in the mol.wt. range of 4,000-6,000, except in the case of H(-Pro-Sar-Gly-)n OH which yielded molecular weights over 20,000.


Synthesis by conventional methods of human growth hormone peptide fragments. I. The synthesis of two protected peptides which correspond to positions 139-146 and 147-156 of the HGH primary structure is described. These peptides prepared by the stepwise procedure, are: Boc-Phe-Lys(Z)-Gln-Thr(Bzl)-Ser(Bzl)-Lys(Z)-Phe-OMe and Boc-Asp(OBzl)-Asn-Ser(Bzl)-His(Dnp)-Asn(OBzl)-Asp(OBzl)-Ala-Leu-OBzl. All protected intermediates were isolated and characterized for homogeneity.


Crystal and molecular structure of a 4-oximino-5-imino-pyrazoline active ester. The crystal structure of an active 4-oximino-5-imino-pyrazoline ester has been determined by single-crystal X-ray diffraction methods. The possible reasons for its high reactivity towards nucleophilic reagents are briefly discussed.


Thermally induced permutations of antigenicity and conformation of arachin (peanut globular protein)*. The reactivity of arachin (principal storage protein of the peanut) with anti-arachin decreased after arachin was heated at certain temperatures. Infrared and circular dichroic spectra of heated and unheated samples of arachin were examined to determine whether conformational modes changed concomitantly with decreased antigenicity. Infrared absorbances of each sample at amide I, II and V bands were essentially identical; however, absorbances at amide IV and VI bands were altered in relative intensities proportionally to the temperatures of treatment. Conformational modes, determined by circular dichroism, gradually increased in content of unordered structure from x-helical and pleated sheet modes relative to the temperature of treatment. These observations are discussed in regard to relationships of the loss of antigenicity to conformatonal changes in heated arachin.


Trinitrophenylation of the bilirubin binding site of human serum albumin. Human serum albumin has been modified with 2,4,6-trinitrobenzenesulphonic acid and picryl chloride in low ratios of reagents/albumin. The derivatives have been investigated by spectrophotometry and by thin layer chromatography of the hydrolysates in order to assess the specificity of the reagents. The same reaction conditions were used to modify albumin previously complexed with bilirubin in the ratio of 1:1. The affinity of bilirubin to the modified albumins was estimated by an improved perozidase method. It is concluded that TNBS and picryl chloride react almost quantity with epsilon-amino groups of lysine on the albumin molecule. The results also suggest that at least on TNBS reactive amino group and at least one picryl chloride reactive amino group are located in or near the high-affinity bilirubin binding site.


Oxytocin analogs with substitutions in postions 3 and 4. Synthesis and biological properties are reported for some analogs of oxytocin with replacements of the isoleucine residue in position 3, i.e., (3-proline)oxytocin and(3-D-alanine)oxytocin, and the glutamine residue in position 4, i.e., (4-D-alanine)-oxytocin and (4-D-leucin)oxytocin. (3-Proline)oxytocin exhibited smaller than0.02 U/MG oxytocic activity, 0.005 plus or minus smaller than 0.001 U/mg rat pressor activity and 0.003 plus or minus 0.0001 U/mg antidiuretic activity. (3-D-Alanine)oxytocin had no agonistic activity in the bioassays tested except for the rat antidiuretic assay (smaller than 0.0005 U/mg). The 4-D-alanine analog showed 0.05 plus or minus 0.003 U/mg oxytocic activity, 0.07 plus or  minus 0.01 U/mg avian vasodepressor activity, and smaller than 0.001 U/mg rat antidiuretic activity. (4-D-Leucine)oxytocin possessed 0.001 plus or minus U/mg rat pressor activity, and showed slight inhibitory properties in the oxytocic and avian vasodepressor assays, inhibiting the oxytocin response in the latter assay by about 60% at a girnibe-to-analog ratio of 1:5000. The activity profiles of the analogs are compared to that of oxytocin and are discussed on the basis of the proposed solution conformation of oxytocin.


Mechanism of glutathione regeneration of reduced pancreatic ribonuclease a. A comparative study was made of the kinetics of glutathione regeneration of reduced pancreatic ribonuclease A, as determined by circular dishroism, sulfhydryl oxidation and the kinetics of reactivation. Four sulfhydryls were reozidizedeactivation. Four sulfhydryls were reoxidized prior to any large circular dichroic changes or recovery of enzymatic activity. The helical and beta segments in ribonuclease were shown to reform at approximately the same rate. The results are discussed in terms of a regeneration mechanism for ribonuclease involving (1) nucleation, (2) polyeptide backbone refolding, and (3) reshuffling of incorrectly paired disulfide bonds.


[The serum concentration of vitamin A in patients with psoriasis vulgaris after oral administration of vitamin A palmitate]. After oral application of vitamin-A-palmitate in male patients with psoriasis we hourly estimated the serum concentration of vitamin A. With rapidly elevating the maximum vitamin A level was achieved in 3-4 hrs but redescended to the initial level within 24 hrs by an exponential decrease. The curve could be fitted to the "BATEMANfunction". The velocity contents k1 and k2 were calculated but were varied individually. The constant b, the time between oral application and the commencement of resorption, was estimated at 30-60 min. The chromatographical analysis of the total vitamin A in all patients yielded a unique ratio of vitamin A-alcohol, -acetate and -palmitate for each hour.


Studies on mode of action of vitamin A.

Studies on mode of action of vitamin A. Effect of feeding 5000,10 000, 20 000, 30 000 and 40 000 I.U. of vitamin A for two days to 25 days old rats has been studied on liver protein, RNA and DNA, liver and plasma lipids and adrenal cholesterol. The incorporation of palmitate- I-14-C into liver and plasma lipids has been studied in vitamin A fed rats. Two  patterns of effects of vitamin A were observed in rats on their liver protein, RNA and DNA and liver and plasma lipids. At lower amounts of vitamin A feeding either the above did not change or were increased, but at higher amounts of vitamin A feeding the above were decreased as compared to the controls. Plasma nonesterified fatty acids were increased and adrenal cholesterol decreased in rats fed 5000 I.U. of vitamin A, but were not affected in rats fed higher amounts of vitamin A. The utilization of palmitate-I-14-C for the synthesis of liver triglycerides and phosphoglycerides was reduced in rats fed higher amounts of vitamin A, but was not significantly different from the controls in rats fed liver amounts of vitamin A. The effects of vitamin A are influenced by the age of the animal as well as the amounts of vitamin A fed. The results show that the effects of vitamin A are exerted by the stimulation of adrenal activity (increased corticoid synthesis).


Thiamine absorption in the rat. ii. intestinal alkaline phosphatase activity and thiamine absorption from rat small intestine in-vitro and in-vivo. The correlations between intestinal alkaline phosphatase (IAP) activity and thiamine absorption and glucose absorption were studied in the rat. An everted sac in-vitro technique was used in adult rats whereas in-vitro experiments were performed in young rats 10 days old. All incubation experiments were done with 14-C-labeled thiamine. The patterns of IAP activity along the small intestines differed greatly between young and adult rats but were closely paralleled by the distribution of active thiamine transport in adult rats and thiamine absorption in young rats, respectively. When IAP was specifically inhibited in adult rats by L-phenylalanine active thiamine transport in-vitro was abolished. No correlation was found between IAP activity and active transport or glucose in-vitro, nor did inhibition of the enzyme in any way affect glucose transport capacity. It is suggested that the enzyme intestinal alkalinephosphatase is involved in the process of active thiamine absorption.


Action in human blood of methoxylated flavones which confer disease resistance on both plants and animals: concept of a dietary conditioned mechanism of defense against disease-1,2. The antiadhesive action of methoxylated flavones on cells in blood of hospitalized patients was significantly associated with calcium, probably at membrane interfaces. This action is consistent with the role of calcium in cell aggregation and disaggregation. These and other recent findings suggest the body has a capacity for an environmentally related dietary conditioned, resistance to disease. The concept is based on evidence that phenylbenzo-gamma-pyrone derivatives, methyoxylated flavonoids and related compounds, synthesized in plants with antiviral, antifungal and bacteriostatic action may be absorbed into the body and attach reversibly to blood cells. In the body, in addition to any potential action against pathogens, certain of these compounds potentiate enzymes which detoxify carcinogenic hydrocarbons, exhibit antiinflammatory activity, exert antiadhesive action on blood cells and show antithrombogenic activity. The evidence indicates that of this class of compounds, a few are broad spectrum in their action, while several others possess one or another of the above functions. Also, some compounds are active in practically all subjects while others are active only in some patients. Specificities appear to be involved in action of the compounds on both pathogens and body processes.


Vitamin c intake and biochemical status in 25 children of a school in Perugia. In 25 schoolchildren (7-15 years old) a survey has been carried out in spring and fall on vitamin C intake by chemical analysis and plasma level of ascorbic acid. The inter-variation in the intake was very great and correspondingly the standard deviation was large. The values obtained by computation with food composition tables agreed with those by chemical analysis. There was no correlation between plasma ascorbic acid and vitamin C intake expressed also per kg body weight. But the values obtained with this study, together with those of other studies, indicate that in children a higher intake of vitamin C is necessary than in adults to achieve a certain plasma ascorbic acid concentration.


Determination of vitamin C (ascorbic and dehydroascorbic acids) in foods and feeds. Ascorbic acid (ASC) is separated by percolating the extract solution through an anionic Sephadex column. After one or two washings with water, the vitamin is oxidized on the column by a p-benzoquinone solution to dehydroascorbic acid (DASC). This latter being actually no acid is eluted as it is formed. The DASC containing eluate is treated with a new colorimetric reagent: 4-Nitro-1,2-Phenylenediamine (NPD). After extraction of the excess reagent with ethyl acetate, the optical extinction is measured at 375 nm. DASC, if present in the extract solution, can be reduced to ASC by dimercaptopropanol prior to chromatography. The method is very specific. The rather simple chromatographic purification can be effected semi-automatically with series of 10 colums (or more).


[Food analysis for balance studies, especially calcium, magnesium, phosphorus and nitrogen]. The calcium-, magnesium-, phosphorus-, nitrogen- and water-contents have been estimated in raw and processed foods (bread and sausages). These results were then compared with the data in food tables. Surprisingly small differences were recorded, since content-deviations of processed foods are equalized in a whole day menu. Thus, food tables proved to be reliable for the calculation of balance and test diets.


Effects of lithium on electromyographic recordings in man. Studies in manic-depressive patients and normal volunteers. (1) EMG investigations in 17 female manic-depressive patients under long-term treatment with lithium salts showed a reduction of the maximal motor nerve conduction velocity (NCV) and of the duration of isolated potentials (IPs) in six cases. These changes, however, were not clearly due to the influence of lithium only. Psychopathology, additional medication, and other variables may have been also responsible for these finding. (2) NCV and IPs as well as the concentration of electrolytes in serum and RBC were determined in seven healthy volunteers before, during, and after lithium administration. NCV was significantly decreased and the duration of IPs slightly increased after 1 week of lithium intake. The magnesium serum concentration increased steadily during the experimental period. (3) Thus, the possibility cannot be excluded that symptoms of fatigue and muscular weakness in lithium-treated patients might be caused at least partially by changes of the peripheral nervous-muscular function.


Polygraphic night sleep pattern during chronic single and multiple neuroleptic dose administration. A comparison was made between the polygraphic night-sleep pattern of chronic schizophrenic patients who were receiving a single dose of neuroleptics at bedtime and between the night-sleep pattern of the same patients receiving the same amount of the same neuroleptic divided into 3-4 doses during daytime. It was shown that the single bedtime dose provoked a significant increase in the mean percentage of the NREM stage 4 and of the mean percentage of the REM state whereas the mean percentage of the NREM stage 2 was significantly decreased.


The effect of chronic lithium application on the mineral content of rat bone and soft tissues. Rats were treated with lithium chloride over 6 weeks. During the experiment, determinations of serum calcium, magnesium and phosphorus revealed no changes due to the therapy. Postmortem examinations of liver, skeletal muscle, and femur minerals as well as bone histology showed these organs to be unaffected by lithium application. Only body weight gain was in part increased by lithium.


[Studies of lithium-induced tremor by means of different measurement methods]. The authors discuss the character of lithium-induced tremor. Three various measuring methods are presented: an accelerometer, a hole-plate and an apparatus based on aimed tapping. A fourth apparatus is proposed. The first three methods were applied on 16 patients who received lithium therapy and on a control group consisting of 22 normal persons. The results were statistically evaluated. For registering the postural component of lithium-induced tremor, the first two methods proved themselves worthy of recommendation in quotidian practice. Frequency and amplitude of lithium-induced tremor till the ninth day of drug administration are discussed - and constitute only one aspect of a bigger, still going on, study.


Phenothiazine effects on cerebral-evoked potentials and eye movements in acute schizophrenics. An investigation was made of the effects of phenothiazine medication on the averaged visual-evoked potentials (AVEP) and on eye movements in hospitalized, young, acute schizophrenic patients. These results were compared with those of normal subjects who were not given medication. AVEP measures included maximum amplitude (Am), frequency of peaks (FOP'S), variability (V) and peak latencies for an early negative peak (N1) and a later positive peak (P6). Eye movement measures included percent of time looking at a stimulus slide, percent of time looking at a figure on the slide, the number of fixations and the percent of cells entered in which fixations occurred. For schizophrenics off and on phenothiazine medication, there were no consistently significant drug effects on any measure except frequency of peaks. Schizophrenics compared to normals had lower amplitudes, greater frequency of peaks, greater variability and lower eye movement scores.


Gas-liquid chromatographic determination of penfluridol in plasma. A new specific technique. Penfluridol is a new long-acting neuroleptic drug, first shown by Janssen et al. (1970) and later proved by numerous clinical investigations. The plasma level data are in agreement with these findings since penfluridol is measurable in plasma of the patients 7 days after the oral dose of 120 mg/week. In summary, we have provided for the first time a rapid, accurate and precise gas-chromatographic method for measurement of penfluridol in the plasma of schizophrenic patients.


Effect of mesoridazine administration and withdrawal on performance in an older age group. Seven subjects, aged 48-62 years, took a placebo capsule nightly for 3 weeks, mesoridazine 10 mg for 3 weeks, and then placebo for 3 weeks. Mesoridazine is a short half-life phenothiazine useful as a hypnotic. Performance was assessed during three experimental sessions on each test day. In spite of subjective sleepiness 20 min after rising, psychomotor performance 1-3 h later was not imparied, except possibly manual dexterity after the first dose. Neither auditory vigilance, nor digit symbol substitution were affected noticeably by the drug at any time of day. Card sorting of varying degrees of complexity was unimpaired, though there was a suggestion that the drug might be associated with better performance on the most complex task.


The effect of vitreous humor on fluid transport by rabbit corneal endothelium. The effects of vitreous humor and some of its components on the function of rabbit corneal endothelium were investigated and compared to those of artificial and natural aqueous humor. The rate of fluid pumping across the endothelium was measured while that layer was in contact with: (1) complete medium, an artificial aqueous solution; (2) pooled rabbit aqueous humor; (3) filtered and (4) unfiltered pooled rabbit vitreous humor; and (5) solid residue from vitreous humor. The relative magnitudes of the rates were: complete medium greater than aqueous larger than or equal to filtered vitreous greater than vitreous larger than or equal to solid residue. A definite adverse effect of unfiltered vitreous and of its solid residue on endothelial pumping was observed. It is suggested that the solid (collagenous) elements in vitreous humor may be responsible for these effects and perhaps for those generically referred to as the "vitreous touch syndrome" in clinical studies.


Optical and neural resolution in peripheral vision. Visual acuity along the horizontal meridian in the peripheral field of vision was determined at a photopic level in two normal subjects. Two types of sinusoidally modulated, monochromatic test patterns of high contrast were used. One was produced directly on the retina by an interferometric technique. The other type was imaged on the retina by the dioptric apparatus of the eye; the resulting image suffered ordinary optical image degradation. The results from the interferometric acuity determinations represent maximal neural discrimination across the visual field. Acuity decreases monotonically toward the periphery, from about 45 cycles per degree in the fovea, to about 0.8 at 80 degrees of eccentricity in the temporal field. The decline is well described by a second-degree polynomial. Acuity for test patterns imaged by the optics of the eye was consistently lower than interferometric acuity. The difference increases toward the periphery. It is attributable to effects of optical aberrations. The discrepancy between optical and neural resolving power on oblique incidence needs to be taken into account whenever results obtained with external, extra-axial stimuli are to be analyzed in terms of retinal architecture.


Effect of pre-exposure fundus temperature on threshold lesion temperatures in the laser-irradiated rabbit retina. The relationship between pre-exposure fundus temperature and the temperature rise which produces a threshold burn was examined in rabbit eyes exposed to an Argon c. w. laser (4,880 A) for 10 seconds. The posterior pole of the eye was surgically exposed and a 20-micron tip diameter probe was inserted into the ocular fundus to measure temperature rises. The temperature rise for threshold burns linearly increased as preexposure fundus temperature decreased, implying a constant threshold temperature. Threshold temperature was indirectly predicted to be 52.4 degrees C. using a system with an estimated error of plus or minus 1/2 degrees C.


Differences in the mechanism of action of medrogestone and cyproterone acetate. In the intact adult rat, medrogestone was found to be effective in causing the involution of the prostate and seminal vesicle. Medrogestone, however, does not function through an antiandrogenic action. In the castrate animal medrogestone was unable to block the stimulating action of exogenous testosterone on the sex accessory organs as shown by effects on tissue weight and DNA synthesis. In addition, medrogestone was unable to block the uptake of labeled androgen into prostatic nuclei. The effectiveness of medrogestone on sex accessory tissue may be accounted for by its ability to lower plasma testosterone levels. This is achieved by inhibiting testosterone biosynthesis. The action of medrogestone was compared to that of cyproterone acetate and it was concluded that these drugs inhibit prostatic growth through two different mechanisms.


Concepts and limitations in the application of radiolabeled antiandrogens, estrogens, or androgens as isotopic scanning agents for the prostate. The distribution of labeled antiandrogens, estrogens, and androgens has been studied in the rat and dog to elucidate the principles and limitations encountered when these agents are used in radioscanning the prostate. The bulk of the label is rapidly cleared in the biliary secretions and in the urine. The concentration of label in the prostate in comparison to other tissues such as the intestines limits the application of these agents in radioscanning of the prostate. The tissue distributions were confirmed by total body radioscans of rats and dogs receiving a labeled 3'-iodinated analog of the antiandrogen flutamide (Sch 13521 or 3'-trifluoromethyl-4'-nitroisobutyranilide).


Tryptophan urinary bladder absorption and bladder cancer. Local vesical absorption of organic compounds may play a role in the pathogenesis of bladder cancer. An associated increased absorption of tryptophan in patients with bladder cancer has been demonstrated.


Rhythmic contractions in the renal pelvis correlated to ureteral peristalsis. Using a transparenchymal pressure catheter and a specially designed DC amplifier, rhythmic pressure variations have been demonstrated to occur in the renal pelvis of dogs. For the hydropenic dog this frequency is constant during the course of all the experiments. The interperistalic interval in the ureter constitutes a multiple of the pelvic pressure variations. The ratio of ureteral to pelvic activity is 1 during osmotic diuresis. The frequency of the ureteral activity was never found to be larger than the pelvic activity. These experiments suggest that the ureteral contractions are correlated to the pelvic activity.


Growth of calcium oxalate crystals. I. A model for urinary stone growth. The kinetics of the crystal growth of calcium oxalate monohydrate has been studied using the technique of seeded crystal growth from stable supersaturated solution. The rate law takes the form minus dc/dt equals kN-2 in which the rate of loss of lattice ion from solution is proportional to the square of the supersaturation. It is proposed that the incorporation of lattice ions into the crystal is governed by a bimolecular surface-controlled reaction step. The rate is independent of the hydrodynamics of the system but is proportional to the solid to solution ratio in the supersaturated solution. The specific rate constant, k (M-minus-1 min-minus-1 [mg/dl]minus-1), is nearly independent of the solid to solution ratio, however. The rate of crystal growth was found not to vary with the calcium to oxalate molar ratio in the range 1.5 to 0.75, although the rate did increase at both higher and lower ratios. The method was found to be simple, rapid, and reproducible and lends itself to the quantitative study of inhibitors of crystal growth.


Cystometry and simultaneous electomyography from the striated uretheral and anal sphincters and from levator ani. For more than one decade, we have used the cystometry-electromyography (EMG) investigation as a clinical method in patients with known or suspected neurologic disorders in whom a defect in bladder emptying, in spite of an active detrusor contraction, is found at cystometry. The electomyographic activity during bladder filling and micturition has also been studied in healthy subjects. Among other things, a voluntary control of the external urethral sphincter relaxation--independent of the degree of bladder filling--was found in most of these healthy volunteers. The cystometry-EMG investigation is easy to perform and gives reliable information as to whether a detrusor-sphincter dyssynergia exists. This information is indispensable for the choice of therapy in neurogenic cases with infravesical obstruction. In patients with upper motor neuron lesions a detrusor-sphincter dyssynergia was found when performing the ice water test. In some cases, the sphincteric contraction was so strong that the ice water was prevented from being expelled by a forceful detrusor contraction. Such false negative ice water tests can be avoided by recording the intravesical pressure when performing the test.


In vitro perfusion of the canine prostate. An experimental model has been developed for perfusing intact canine prostates in vitro. The glands maintain normal anatomic and histologic appearance and function in a physiologic fashion. Estradiol has been shown to augment testosterone uptake by the prostatic cell. The implications of these findings are discussed.


Ureteral reimplantation. The effect of proximal urinary diversion and bladder defunctionalization in dogs. The results of two animal studies are presented in which ureteroneocystostomy is performed in the absence of urinary flow. No stents were used. In Group 1 ureterovesical stenosis resulted in 2/7 defunctionalized ureters in animals with an otherwise intact bladder. In Group 2 seven animals had bilateral urinary diversion with reimplantation of 14 diverted ureters into a defunctionalized bladder. Ureterovesical stenosis did not occur in any in this second group. There was a 9.5 per cent incidence of ureterovesical stenosis over-all. This would not support the clinical impression that "dry" ureteroneocystostomy inevitably results in ureterovesical stenosis.


Ischemic heart disease and pulmonary ventilatory function. The results of spirometric examinations on 4, 331 Israeli male civil service employees, aged 45 years or more, were analyzed according to the presence or absence of certain aspects of ischemic heart disease. Vital capacity was lower in individuals with a previously history of a heart attack, in those with definite or suspected angina pectoris and in those with ECG evidence of myocardial ischemia, probable or possible myocardial infarction, left bundle branch block or nonspecific T wave changes in subjects without these findings. The differences were small, but statistically significant. Vital capacity was lower in subjects with a recent history of a heart attack (within three years) than in those whose heart attack had occurred more than three years prior to the examination. The ratio of forced expiratory volume in the first second to forced vital capacity was not significantly different between individuals with or without a past history of heart attack, angina pectoris or ECG evidence of coronary heart disease.


Cardiopulmonary disease in Manson's schistosomiasis. Five patients with cardiopulmonary manifestations of Manson's schistosomiasis are described. Two patients had pulmonary hypertension, two had cyanosis and one had the very rare combination of both. The results of routine pulmonary function tests--not sufficiently studied in this form of schistosomiasis--are discussed in detail. Aside from a tendency to hyperventilate, found in all cases, the only significant abnormality encountered was hypoxemia due to increased right-to-left shunt in the cyanotic patients. Although more studies are needed, the results suggest that the pulmonary lesions are mainly vascular in nature. The pathogenesis of cyanosis in this disease is briefly discussed.


Levels of serum complement components in patients undergoing renal dialysis. Following acceptance to a renal dialysis therapy program, 13 patients underwent serial examination of the serum complement system for periods of 6 to 12 months. Serum levels of C3 and C4 were examined at monthly intervals before the first dialysis of each month. The patients suffered from various primary renal diseases, including glomerulonephritis, obstructive uropathy with chronic pyelonephritis, nephrosclerosis and chronic nephropathy of undetermined nature. Levels of serum C3 were depressed at some time during the study period in all patients. Serum C4 levels were normal. The depression of serum C3 levels was significant and prolonged in nine patients. There seemed to be no relationship between the nature of the basic disease and the depression of serum C3 levels. Caution should be exercised in attributing depressed C3 levels to a particular type of underlying renal disease in patients on renal dialysis.


Overt hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency: a survey in general practice. The records of 129 patients with glucose-6-phosphate dehydrogenase deficiency from two general practices were reviewed for overt hemolysis. There were 25 such cases: 14 were diagnosed as favism; 10 were associated with various combinations of drugs, or with fever, infection, acidosis or the neonatal state; and one was of undetermined cause. Over the years 1952-72, these patients had been challenged on 756 occasions with potentially hemolytic drugs. The low incidence of overt hemolysis after antipyretic preparation is noted, as is the danger of nitrofurantoin. The clinical setting was an important determinant of whether hemolysis would occur after drug administration. Fever seemed to be a particularly significant factor. Quantitative determinations of enzyme activity in 18 patients confirmed the reliability of the screening method used. There was no correlation between the enzyme levels and the occurrence of overt hemolysis.


High- and low-risk blood donors in Jerusalem: a survey of the hepatitis B antigen (HBsAg). A survey of the hepatitis B antigen (HBsAg) in Jerusalem blood donors revealed an overall prevalence of 0.75%, with a significant difference between males (0.90%) and females (0.38%). Analysis according to ethnic groups indicated that immigrants from North Africa had the highest prevalence (3.18%) and immigrants and tourists from North America and Europe the lowest (0.35%). Analysis according to volunteer, paid professional or family replacement categories indicated that a fourfold increase in the HBsAg prevalence for family donors (0.38 to 1.77%) coincided with the discontinuation of payment to professional donors and intensification of recruitment efforts toward volunteers and replacement donors. Case investigation of the HBsAg-positive donors within the family replacement group revealed that 24% were, in fact, commercial donors covertly engaged by the families of patients to fulfill replacement obligations. The present study illustrates how a community blood program which includes nonvoluntary donations, such as family replacement donations, incurs the risk of inadvertently introducting commercial blood donors into donor population. The findings support the premise that a 100% volunteer blood program is the most reliable guarantee for maintaining a blood supply from healthy donorswith a minimal risk of infectivity from hepatitis.


Adjustment and rehabilitation problems of children and adolescents with growth retardation. I. Familial dwarfism with high plasma immunoreactive human growth hormone. Nine children and adolescents with the syndrome of familial dwarfism and high plasma immunoreactive human growth hormone were assessed by means of a battery of psychological tests, and they and their parents were interviewed with the aim of studying the problems of adjustment and rehabilitation in this group of patients. The group as a whole showed a lower-than-average intelligence quotient and a distinct deficiency in visuomotor functioning. Although this type of dwarf is well proportioned and without major malformations, his markedly small stature and limited physical endurance cause various problems, including those of mobility, clothing, and accommodation to public transportation and normal-sized furniture in school and at work. Psychological problems include intrafamily relationships and the attitudes encountered in school, in social situations and at places of employment. It is concluded that these patients need the specialized counseling of a centralized rehabilitation center which offers a combined program of medical care, psychological support and assistance with such problems as schooling, choice of occupation and the finding of suitable employment. It is suggested that the rehabilitation problems and needs of all dwarfs are similar, irrespective of the etiology of the dwarfism.


Individual aspects of cancer cells: special karyographic technique. The contours of interphasic nuclei of normal and cancer cells are transcribed using a special karyographic technique. The resulting undulating lines are analyzed and compared, and their relationship to the malignancy, and individuality and clonal constitution of different tumors is discussed. The possibility of establishing an "identity card" for cancer cells is considered.


Adenocarcinoma of the cervix in Jewish women: a clinicopathologic study of seven cases. During the 14-year period from 1959 to 1973, 60 primary cervical carcinomas were diagnosed at the Kaplan Hospital; 53 were squamous cell carcinomas and seven, adenocarcinomas. The ages of the patients with cervical adenocarcinoma ranged from 22 to 70 years, with a mean of 51.2 years. Postmenopausal bleeding was the most common symptom. One patient was in clinical stage 0, three were in stage I and three in stage II. All patients were treated by irradiation, and four underwent total hysterectomy in addition. Two patients died of cervical adenocarcinoma 16 and 24 months after establishment of the diagnosis, four are alive one to two years after diagnosis, and one has been lost to follow-up. Histologic examination revealed one in situ adenocarcinoma, four papillary and two nonpapillary tumors. Cervical adenocarcinoma in Jewish women presents clinicopathologic features similar to those described in non-Jewish populations. The only significant difference between the two populations appears to be that adenocarcinomas account for a higher proportion of all cervical carcinomas in Jewish than in non-Jewish women.


A case of severe human coccidiosis in Israel. A 51-year-old woman presented with intermittent diarrhea and marked loss of weight. Stool examination and duodenal intubation both yielded coccidian oocytes of Isospora belli. The patient responded to treatment with Septrin (trimethoprim and sulfamethoxazole), 2 g daily for three weeks. This is the first reported case of severe human coccidiosis in Israel.


A program for preventive ophthalmology in Israel: possible implications for prevention units in other specialized branches of clinical medicine. A program is proposed for a prevention unit in ophthalmology in a medical school situated in a technologically developed country where degenerative diseases play a major role in the etiology of eye disease. The relationship of such a unit to the corresponding curative departments, to the departments of social medicine and medical ecology, to the Ministry of Health and to the corresponding professional body are described. The role such a unit may have as a forerunner of the formation of similar units in other specialities of medicine is emphasized.


Esterase XIX. Biochemical and ultrahistochemical investigations of the non specific esterase in nuclei from mouse liver. The present investigations reveal that the non specific esterase from mouse liver nuclei is exclusively located in the perinuclear cistern and that the nuclear chromatin does not contain any esterase as a rule. However, esterase is associated with lipid droplets which are seldomly found within nuclei. Two different esterases are demonstrated with the employed substrates in the nuclear envelope. It is exemplified that the esterase, found in isolated nuclei, can neither be understood as qualitative nor as quantitative equivalent of the esterase demonstrated ultrahistochemically at nuclear membranes.


Ultrastructural detection of lectin receptors by cytochemical affinity reaction using mannan-iron complex. A two-step affinity reaction is described for electron microscopic demonstration of the Concanavalin A as well as the Lens culinaris lectin receptors by means of the yeast mannan-iron complex. First the tissue was incubated in the lectin. Afterwards the incubation in the yeast mannan-iron complex was performed and reaction takes place between the still free second sugar binding site of membrane bound lectin molecules and the polysaccharides. This membrane receptor-lectin-polysaccharide complex is revealed by the electron dense iron core of the yeast mannan-iron complex. The specificity of the reactions could be demonstrated by addition of the hapten or by incubation in the yeast mannan-iron complex only. The proposed technique has proved useful for demonstration of lectin receptors in the small intestine.


Demonstration of catecholamines in peripheral adrenergic nerves in stretch preparations with fluorescence induced by aqueous solution of glyoxylic acid. Fluorescence induced by aqueous solution of glyoxylic acid and formaldehyde-induced fluorescence of catecholamines were compared for the demonstration of peripheral adrenergic nerves in stretch preparations. Glyoxylic acid was better than formaldehyde for the demonstration of the adrenergic nerves. On the other hand, the formaldehyde was better than glyoxylic acid for the demonstration of biogenic amines in cell bodies.


[Quantitative 125-I-autoradiography of individual cells (author's transl)]. Iodine 125, an emitter of beta-radiation with an energy lying between that of tritium and carbon-14, is investigated for its applicability in quantitative autoradiography. Absorption and geometric factors of radiation are elucidated. From this, appropriate measuring conditions are derived. The simultaneous exposure of radioactive standard sources permits the evaluation of absolute amounts of radioactivity. Standard cells with labelled membranes are a suitable source of reference taking into account the physical properties of the isotope. Sheep red blood cells are examined for their suitability as standard cells after enzymatic radioiodination. The absolute number of antigenic substances on the surface of single cells is obtained by determining the specific activity of the labelled antibody molecules, and by measuring the silver grain densities of the cells under investigation and of the standard cells. The radioactivity per standard cell can be assessed by conventional procedures. The new method is applied to the quantification of membrane-bound immunoglobulin molecules of the IgG-type on single human lymphocytes. The determination of an immunologic saturation of the labelled antibody is essential for this purpose. On the lymphocytes of a normal person and of a patient with chronic lymphatic leukaemia quite different amounts of immunoglobulins have been evaluated.


Histochemical studies of 3 beta- and 20alpha-hydroxysteroiddehydrogenase in the adrenals and ovaries of the nu/nu mouse. Adrenal glands and ovaries of nu/+ and nu/nu female mice were examined histochemically throughout the postnatal life for changes in distribution, intensity and appearance of activities of 3 steroid-converting enzymes. While the 3beta-OH-steroid- and pregnenolone-dehydrogenase did not reveal any difference, the 20alpha-hydroxysteroid-dehydrogenase (20alpha-OH SDH) showed a constant behaviour: the onset of the enzyme activity was detectable in the adrenals of nu/+ mice after the second week of age, in nu/nu mice 3--4 weeks later. The localization of 20alpha-OH-SDH was strictly confined to the zone of small cells, a zone lying between the x-zone and the zona fasciculata. In nu/+ mice, after reached sexual maturity at about 6--8 weeks of age, the enzyme progressively disappeared from the adrenals and simultaneously appeared in the ovaries. In nu/+nu mice, which had been kept separated from mating animals, the 20alpha-OH SDH persisted in adrenals even in adult stages. After pregnancy, both--nu/nu and nu/+, showed 20alpha-OH SDH-activity in ovaries and none in adrenals. In both, the enzyme was localized in involuting corpora lutea, whilst in nu/nu it was also present in the intersitial cells. This study indicates no disturbance in the formation of progesterone, but the process of its degradation, as indicated by 20alpha-OH SDH-activity, is definitely different in nu/+ and nu/nu.


Are all the neuronal nuclei polyploid?

Are all the neuronal nuclei polyploid? The DNA analysis of rat brain nuclei by two independent cytochemical methods, namely microfluorometry and UV-absorption, brings completely different results to those published previously by many investigators. The neuronal nuclei possess twice as much DNA as the glial nuclei.


[Esterase XX. Disc-electrophoretic investigations on the polymorphism of the esterases of the house mouse (author's transl)]. For the further clarification of the polymorphism of mouse-esterase and its hormonal control, which in part have not yet been fully comprehended, disc-electrophoretic analyses of eight organs were made, using a strain with the Tfm-mutation. In addition, quantitative assays of esterase activity as well as histochemical studies were performed. The individual organs are characterized by a specific banding pattern of esterase, which is essentially conditioned by the diverse activity of a limited number of bands. Partly these may be regarded as primary gene products, partly they seem to be secondary modifications. The few incidences of band-linkage justify the expectations, that further gene loci will be discovered. In four organs of Tfm-mutants a lower esterase activity was found than in the controls, which was especially distinct in the kidney. The behaviour of the testosterone-dependent bands in the kidneys of Tfm-mutants seems to indicate two different mechanisms of the effect of testosterone on these bands.


On the soluble phase of adrenergic nerve vesicles: correlation of matrix density and biochemical composition. Highly purified sympathetic nerve vesicles isolated from bovine splenic nerves were treated by hypo-osmotic shocks, freeze-thawing or incubation in the absence or presence of ATP and MgCl. The vesicle preparations were then studied morphologically by electron microscopy and their content of noradrenaline (NA), and soluble proteins analyzed biochemically with special regard to dopamine beta-hydroxylase (DBH). Hypo-osmotic shocks released about 25 per cent of the NA and protein content and about 8 per cent of the DBH activity. This treatment induced swelling of the vesicles but their membranes remained unruptured and they still contained dense cores. Freeze-thawing released about 35 per cent of the NA, 25 per cent of the proteins and 11 per cent of the DBH. After the latter treatment some matrix material still remained in most vesicles but many were less stainable than the intact vesicles in cold control preparations. During incubation at 30 degrees C in an isotonic sucrose-phosphate medium for 30 min the vesicles released most of their NA and soluble DBH activity as well as much of their matrix density. After incubation at 37 degrees C for 30 min most vesicles appeared translucent. After incubation at 30 degrees C for 30 min in the presence of ATP and MgCl the vesicles lost most of their original NA content but retained their DBH activity and most of their matrix density. The results indicate that there is not always a correlation between NA content and retention of matrix density which suggests that DBH might be a component of a macro-molecular complex responsible for the staining reaction taking place in the maxtrix of NA depleted vesicles. This hypothesis is further supported by the finding of striking similarities between DBH isolated from chromaffin granules and the granular and fibrillar material surrounding the nerve vesicles after depletion.


Histochemical study on the distribution of some enzyme activities in the vagal and facial lobes of the goldfish, Carassius auratus. The histochemical localization of six enzymic activities (acetylcholinesterase, pseudocholinesterase, monoamine oxidase, lactate dehydrogenase, succinate dehydrogenase and glucose-6-phosphate dehydrogenase) has been studied in the vagal and facial lobes of the goldfish, Carassius auratus. These encephalic centers are hypertrophic in Cyprinidae, corresponding to the dominance of gustatory function. Acetylcholinesterase shows a complex laminar distribution in the vagal lobes and a peculiar cellular localization in vagal motor neurons. Monoamine oxidase activity is mainly evident in fibrous tracts coming to or leaving from the lobes. Among oxidative enzymes examined, lactate dehydrogenase and succinate dehydrogenase exhibit distribution patterns respectively similar to those observed for acetylcholinesterase and monoamine oxidase. Some features on enzymes distribution in the gustatory centers of Carassius are in agreement with the enzymatic patterns well known in higher vertebrates.


Canine polypoid cystitis.

Canine polypoid cystitis. The clinical, laboratory, and radiographic characteristics of polypoid cystitis in 2 dogs were similar to those commonly associated with neoplasms of the urinary bladder. Gross appearance of the polyps did not permit differentiation between inflammation and neoplasia; microscopic examination of excised tissue was required to establish a definitive diagnosis. Following surgical extirpation of the polyps, remission of clinical signs was induced by prolonged antibacterial therapy.


Neoplasms of the canine urinary bladder. Evaluation of histologic data obtained from 90 breeds of dogs with 3,837 neoplasms collected over 10 years (1961-1971) revealed 21 cases of urinary  bladder neoplasmia in 14 breeds of dogs. There was no breed predispostion. The mean age of dogs with urinary bladder neoplasia was 9.5 years; 6 were males, 13 were females, and 2 were spayed females.


Treatment of discospondylitis in the dog. A combination of spinal cord decompression, spinal column immobilization, and systemic antibiotic therapy was used to treat discospondylitis in 30 dogs. Recovery was complete in 7 of 9 dogs with cervical involvement and in all 21 dogs with thoracolumbar involvement.


Pyruvate kinase deficiency anemia with terminal myelofibrosis and osteosclerosis in a beagle. A 15-month-old male Beagle with chronic hemolytic anemia was found to have erythrocytic pyruvate kinase deficiency and, terminally, myelofibrosis and osteosclerosis. The dog's erythron was studied by procedures that enabled close comparison with congenital hemolytic anemia (pyruvate kinase deficiency) of Basenji dogs. The affected dog's sire, dam, and one littermate--each clinically and hematologically normal--were found to have 50% reduction in erythrocytic pyruvate kinase (PK) activity.


A field study on embryo transfer in cattle. Thirty-five 4-day-old embryos were surgically collected from 5 Fleckvieh and 3 Gelbviehheifers. The embryos were transported by air on the same day to a distant rach where 34 embryos were surgically transferred via the flank into recipient cows. Nineteen recipient cows were diagnosed pregnant at approximately 50 days.


Cysticercosis from Taenia hydatigena in feedlot lambs. A feedlot enterprise fattened 50,000 lambs from August, 1973, through May, 1974. Of those that died during that period, 96 were necropsied; of this number 27 (28%) were infected with cysticeri. The parasites produced bore channels in livers and bladder worms on viscera. Some lesions were assessable for their duration of infection.


An epizootic of bovine cysticercosis.

An epizootic of bovine cysticercosis. In March, 1973, a large feedlot near Phoenix, AZ, reported an increased incidence of bovine cysticercosis. Approximately 10% of cattle sent to slaughter from January to April, 1973, were infected with the cysticercus stage of Taenia saginata. One employee who worked at the feed mill and loaded hay in the fields was also found to be infected with T saginata. Recommendations for control of similar epizootics included educating employees about mode of transmission and improved personal hygiene, the inauguration of a surveillance program that included examination of employees prior to employment and periodically thereafter, maintenance of animal source and destination records, restriction of unauthorized personnel to critical areas, and periodic microbiologic assay of water supply.


Abnormal bone development and lameness associated with secondary copper deficiency in young cattle. Lameness in a group of 5- to 12-month-old calves was found to be clinically, radiographically, and pathologically associated with abnormal bone development of the distal growth plates of the metacarpus and metatarsus. Copper concentrations in serum and liver were low. Serum calcium, phosphorus, and alkaline phosphatase values were normal. In pasture forage samples, sulfate, zinc, and molybdenum concentrations were high, whereas copper, calcium, and phosphorus concentrations were normal. Red blood cell (RBC) counts and hemoglobin values were within normal limits. Radiographic findings included a widened zone of cartilage and lipping of the medial and lateral areas of the physeal plate. Histologic findings included focal widenings of the growth plate consisting of tongues of uncalcified cartilage.


Hypotrichosis in Miniature Poodle siblings. Progressive hypotrichosis was detected in 2 silver male Miniature Poodle siblings at 5 weeks of age. A male and 2 female siblings had normal black coats. The sire, a 3-year-old black Miniature Poodle, and the dam, a 2-year-old silver Miniature Poodle, also had normal coats. Microscopically, the hypotrichotic skin had accumulations of keratotic debris and melanin in dilated hair canals and melanin deposits in and around inactive hair bulbs. Sex-linked or sex-limited inheritance may have been involved, inasmuch as both affected dogs were males.


An ultrastructural study of implanting mouse blastocysts: coated vesicles and epithelium formation. Electron microscopial techniques were used to study mouse embryos at implantation stages (5 1/2 days post coitum). Evidence was obtained indicating that trophoblast cells remove uterine luminal epithelial cells by phagocytosis. Small coated vesicles very probably play an important role in the process of digestion of uterine cells by the trophoblast. Two types of endoderm cell were present: the embryonic endodermal cells contained organelles appropriate to a nutritive pathway; the extra-embryonic endodermal cells were relatively poorly developed compared with those of the embryonic endoderm, and remained as a discontinuous layer. The ectoderm contained few organelles. Epithelium formation is described. Junctions only develop between cells in the same germ layer except for occasional ones, including desmosomes, between trophoblast and uterine epithelial cells. The author wishes to thank Professors J.M.F. Landsmeer and W.T. Daems for their stimulating discussions during this research project and for their helpful comments during the preparation of the manuscript. The Laboratory for Electron Microscopy kindly provided full facilities. The assistance of Mr J. Tinkelenberg in the preparation of the drawing (Fig. 1) is acknowledged. Thanks are also due to Mrs 2. seeger for reading the English manuscript and to Miss Ria Stokman for typing it.


The fine structure of proliferating cartilage cells: structural changes in an experimental model. Extensive development of the rough endoplasmic reticulum and comparatively less developed Golgi membranes were seen in the cells of chondrocyte clusters which had formed in the vicinity of cartilage defects produced by intra-articular papain and cortisone injections. These cells frequently showed myelin-like membranous figures. These figures were seen either close to the cell membrane, or between cells, or connected to the nuclear envelope or the endoplasmic reticulum. The hypothesis is advanced that the myelin figures are made from redundant material which was not used for membrane formation. Cortisone, which is known to interfere with mitochondrial function and general metabolic processes, could have been responsible for the deficiency in membrane differentiation and transfer. This investigation was supported by grants from the Orthopaedic Research and Education Foundation and from the Research Evaluation and Allocation Committee of the School of Medicine, Univeristy of California, San Francisco.


Temporal and spatial aspects of oestrogen-induced RNA, protein and DNA synthesis in delayed-implantation mouse blastocysts. The temporal and spatial parameters of oestrogen-induced increases in RNA, protein and DNA synthesis were investigated autoradiographically in mice undergoing experimental diapause. The tritiated precursors, uridine, amino acid hydrolysate and thymide, were instilled into uterine lumen for a 15 minute pulse at various times after subcutaneous oestrogen treatment. RNA synthesis increased between 15 and 30 minutes, and protein synthesis between 30 and 45 minutes, after oestrogen administration. DNA synthesis did not increase up to 24 hours after oestorgen. No spatial correlations could be made between trophoblastic giant cell transformation and the RNA and protein synthesis although both are induced by oestrogen.


Postnatal growth of the dog heart.

Postnatal growth of the dog heart. We have found that, in the dog at birth, the right ventricle weighed significantly more than the left. At 3 days the left ventricle weighed the same as the right ventricle. No evidence for postnatal atrophy of the right ventricle was found--the right ventricle simply gained weight at a much slower rate than the left. The left ventricle weighed significantly more than the right at 7,9,11,13,15 and 17 days.


The development of the olfactory mucosa in the mouse: electron microscopy. The development of the olfactory epithelium from the 10th day of gestation of postnatal life has been examined electron miscroscopically in the mouse. At 10 days' gestation the epithelium is already differentiated into dark and pale cells, the former representing embryonic stem cells and the latter the developing receptors. Axons are also visible at this stage. At 11 days the first signs of dendrite formation appear, and at 12 days spheroidal terminal swellings containing numerous microtubules are present at the apices of receptor dendrites. Centriole clusters also appear in the receptor cell bodies and dendrites. From the 12th to the 16th day of gestation a few cilia are formed on the receptor endings. Final steps in the maturation of differentiating receptors begin on the 17th day of gestation, when membranous organelles and lysosomes increase greatly in numbers. However, immature receptors can still be found in the base of the epithelium in postnatal life. Supporting cells are first recognizable on the 17th day of gestation, derived apparently from the remaining stem cells. At the same time differentiated basal cells and glands of Bowman begin to appear. In the early develoment of the olfactory nerve bundles the axons have large and varying diameters, but later on axonal sizes are progressively reduced and the adult size range is achieved at about 18 days of gestation. The significance of these findings is discussed.


Histochemically detected differences in cultured sympathetic neurons. Fetal or newborn rat and guinea-pig sympathetic ganglia were cultured in Rose chambers. After periods of up to 14 days in vitro, cultures were processed for catecholamine fluorescence or acetylcholinesterase histochemistry. The two types of neuron previously identified showed different histochemical reactions. The less frequent, smaller Type I cells contained catecholamine but did not stain for acetylcholinesterase. These cells may be immature. The more common Type II cells showed reactions for both catecholamine and acetylcholinesterase and in this respect resembled mature ganglion cells.


The effect of in utero decapitation on the morphological and physiological development of the fetal rabbit lung. A study has been made of the consequences of in utero decapitation on the morphological and physiological development of the fetal lung. Fetal rabbits were decapitated in situ at 22 days, without losing any amniotic fluid, and allowed to continue their development with their undamaged littermates as controls. Such decapitation, of course, removes the pituitary and so interferes with adrenal cortical development. Morphological studies showed an interference with lung development in that, although the number of alveolar saccules increased normally, their walls failed to thin. In the decapitated fetuses, a reduction in the number of lamellated bodies per Type II pneumonocyte was found at each age studied; while dense, homogeneous bodies were more numerous. The normal disappearance of glycogen in the Type II pneumonocytes of the decapitated fetuses was retarded. Physiological studies supported these findings. In control fetuses allowed to breathe for a while the Bubble Stability Ratio increased rapidly from day 26 to reach a maximum at 28 days; whereas, in the decapitated ones, bubble stability was not apparent before day 28 and by the 29th day had reached a maximum which was lower than that of the controls. In the control fetuses, lecithin was detected in lung fluid from 26 days on, and in stomach fluid from 29 days. It is argued that lung development must be, at least in part, under the control of the fetus' own pituitary-adrenal axis.


Observations on the structural and innervation of the rat snout. Light and electron miscroscopy were employed to study the structure and innervation of the rat snout. The hairless skin at the tip of the snout was covered in epidermal ridges similar to the ridges seen on primate finger skin. Three types of nerve ending were observed in relation to the surface of snout: corpuscular, found in dermal papillae between epidermal rete ridges: hederiform, found in relation to Merkel cells at the base of the rete ridges; and free, which entered the epidermis from the sides and top of the dermal papillae. The evidence suggests that there may be two ultrastructurally distinct intraepidermal nerve fibres.


The effects of late ovariectomy on the proliferation and differentiation of the uterus of the pregnant rat. The effects of ovariectomy at day 12 of pregnancy on the proliferative activity of the uterine epithelium, metrial gland and uterine muscle in the rat were studied by autoradiography in animals killed one hour after a single injection of tritiated thymidine. The results were amplified by histological and histochemical studies. One day after operation epithelial proliferation was impaired in the ovarectomized animals. From 16 days onwards, however, proliferative activity was at a lower level in controls than in the ovariectomized animals. Three days after ovariectomy uptake of tritiated thymidine by metrial gland cells was less than in the controls. The metrial gland became smaller after ovariectomy and showed histological and histochemical changes from the normal pattern. The increased thickness of the uterine muscle in the ovariectomized animals from the 16 day stage onwards was not associated with any significant change in the labelling index of the muscle cells. The results are discussed in relation to the changes in endocrine environment which may occur after ovariectomy.


Craniofacial variability and its relationship to disharmony of the jaws and teeth. Examination of size and shape changes in the skulls of growing dogs and related canidae indicates that dental irregularity and jaw disharmony result when the growth pattern of the skull as a whole departs too widely from the norm.


Cartilage fibrillation at the ankle joint in Liverpool necropsies. The articular surfaces have been examined in 45 left ankle joints from a random series of adult necropsies in the city of Liverpool. Foci of overt fibrillation, with frank splitting of the articular cartilage surface, were extremely common in the ankle joint and were often already apparent in young adults. With increasing age overt fibrillation tended on the whole to become extensive, but this tendency was partly obscured by considerable variation between individuals. It initially and especially affected the periphery of the cartilage sheets and the boundaries between the central and malleolar articulation territories. Possible explanations for this peripheral susceptibility are discussed. One or more sites on the non-peripheral parts of the lateral and medial malleolar surfaces were next in order of susceptibility. The central territory of the articulation was the least susceptible to overt fibrillation. Minimal fibrillation, with a very superficial splitting of the cartilage surface, could occur at any site on the ankle joint surfaces. With increasing age, extensive involvement of the central territory by this minimal change was much more common than extensive overt fibrillation here. The surface markings of minimal fibrillation sometimes showed a macroscopially apparent orientation en face. In one sort these were parallel to flexion-extension movement and consistent with track markings from abrasive-adhesive wear. In a second sort they were parallel to the dominant en face orientation of the superficial cartilage collagen. The topography and natural history of cartilage fibrillation at the ankle joint is discussed with reference to Liverpool data from other joints. Some of the older ankles showed peripheral segments of fibrous tissue-covered cartilage loss. This feature was attributed to "ageing" rather than osteoarthrosis. Only 1 of 20 left ankles from subjects more than 70 years old showed any region of full-thickness uncalcified cartilage loss with abrasive wear of 'osteoarthritic' type. Thus it would seem that in the majority of the Lverpool population the articular cartilage of the normal ankle joint has a high resistance to the type of vertical wear found in clinically demonstrable osteoarthrosis. The practical implications of this conclusion are discussed.


Modification of seizure disorders: the interruption of behavioral chains. This study investigated the effects of interruption and differential reinforcement on seizures in children. Seizures were conceptualized as the terminal link in a behavioral chain, resulting in a strategy aimed at identifying and modifying behaviors that reliably preceded the seizure climax. Seizure frequency was reduced in four of five subjects, whereas the frequency of preseizure behavior was reduced in only three subjects. Parents and school personnel were successfully used as change agents.


Some ethical considerations of short-term workshops in the principles and methods of behavior modification. Workshops and seminars to expose different sectors of the professional community to the principles and applications of behavior modification are briefly discussed. The possible misapplication of procedures by conference participants, whose only exposure to behavioral methods has been at these workshops is viewed as a potentially serious ethical issue. It is suggested that the goals of such seminars and workshops must be clarified, and methods of evaluation of the participants' skills devised, lest we contribute to the misapplication of procedures and to the criticism that behavioral methods are unethical approaches to treatment.


The aversive control of excessive alcohol consumption by chronic alcoholics in the laboratory setting. The efficacy of several methods of aversive control of excessive alcoholic drinking was investigated in a semi-naturalistic setting that permitted objective measurement of the drinking behavior of chronic alcoholics. Studies 1A and 1B compared an excape-conditioning precedure with a control procedure in which aversive electrical shocks were administered before drinking. Neither procedure effectively decreased subjects' pretreatment, baseline alcoholic drinking behavior. In Study 2, aversive response-contingent shocks effectively suppressed alcoholic drinking, but drinking subsequently returned to its former levels after withdrawal of punishment. Self-administered shock appeared to be as effective as experimenter-administered punishment  for controlling drinking, even  when the punishment contingency was faded out over time. Study 3 replicated the suppressant effect of punishment, and demonstrated that contingent shock was significantly more effective than yoked, noncontingent shock. A direct comparison of self-versus experimenter-administered punishment suggested a possible slight advantage for the latter.


Some structural aspects of deviant child behavior. Covariation within behavior repertoires of problem children were examined. Two boys, referred for psychological help, were observed both at school and at home for about 3 yr. A coded observation system permitted scoring of 19 child-behavior categories and six social-environment categories. After a two-month baseline, behavior categories were intercorrelated, demonstrating that each child showed a group of behaviors that covaried. These groupings were specific to the home and school settings. Contingency management procedures were then applied to each child's problem behaviors in one setting. Next, a reversal phase was instituted, followed by resumption of the initial contingency management phase. These three phases lasted seven months, until the end of the children's public school terms. Results showed that the baseline group of covarying behaviors continued to covary over the three experimental phases. The children then entered a remedial education setting for three summer months, and then returned to schools and were observed in follow-up for 2 yr. The baseline group of behaviors continued to covary during both phases. The behavior covariations could not be accounted for on the basis of temporal relations between the behaviors and social enviroment categories. Although no behavior covariations extended across either child's home and school settings, contingency management procedures produced across-setting effects.


Punishment of self-injurious behavior using aromatic ammonia as the aversive stimulus. Punishment with aromatic ammonia was used to eliminate self-injurious behavior of an autistic woman during experimental sessions. The effects were reversible but were limited to experimental sessions until staff used the ammonia on the ward at all times.


A comparison of three staff-management procedures. Even though administrators must have effective staff-management procedures to ensure implementation of desired programs, many traditional staff-management proceudres remain unevaluated. This study investigated the effectiveness of three such procedures. The administrator of an institution for the retarded (1) sent a memo instructing all staff to lead daily recreational activities, (2) sponsored a workshop teaching staff to lead such activities, and (3) assigned staff activity leaders and provided performance feedback to staff by publicly posting the daily average number of active residents on each ward. Neither the memo nor the workshops motivated staff to lead activities, but after staff were scheduled to lead such activities and given performance feedback, the average daily number of residents engaged in activities on four wards for 95 retarded persons increased from seven to 32. The administration of this facility has adopted similar procedures to maintain such activities on all wards.


Differential reinforcement of other behavior and noncontingent reinforcement as control procedures during the modification of a preschooler's compliance. Differential reinforcement of other behavior (DRO) and noncontingent reinforcement were compared as control procedures during the modification of a 3-yr-old preschooler's compliance. The recorded reinforcer was teacher proximity (within 3 ft (0.9) of the subject for at least 5 sec) which was often accompanied by positive verbal comments that varied in content across experimental conditions. The verabal content during contingent reinforcement might have been: "Thank you for picking up the blocks"; during non-contingent reinforcement: "You're wearing a pretty dress"; and during DRO: "I don't blame you for not picking up because it isn't any fun". Contingent reinforcement increased compliance in all manipulation conditions. Noncontingent reinforcement decreased compliance during two reversal conditions. However, the behavior was variable and did not decrease to the low levels reached during the two DRO reversals.


Effects of within-stimulus and extra-stimulus prompting on discrimination learning  in autistic children. Two different prompting procedures to teach visual and auditory discriminations to autistic children were compared. The first involved presenting an added cue as an extra-stimulus prompt. This required the child to respond to both prompt and training stimulus. The second involved the use of a within-stimulus prompt. This consisted of an exaggeration of the relevant component of the training stimulus and thus did not require that the child respond to multiple cues. The results indicated that (1) children usually failed to learn the discriminations without a prompt, (2) children always failed to learn when the extra-stimulus prompt was employed but usually did learn with the within-stimulus prompt, and (3) these findings were independent of which modality (auditory or visual) was required for the discrimination.


Plasma volumes and constituents of heat-exposed men before and after acclimatization. Five men underwent a 2-wk exercise regimen and were then exposed to 45 degrees C db, 28 degrees C wb, wind speed 1 m/s for 12 h while at rest. Body weight was maintained with 0.1% saline. One week later the exposure was repeated without rehydration. After heat acclimatization, the 12-h experiments were repeated. Frequent body weights, rectal temperatures, and venous blood samples were obtained. Results indicated that hemodilution upon acute heat exposure is partially due to protein influx into the vascular volume and the hemodilution allowed considerable loss of body water before plasma volume returned to preexposure values. Water within the vascular volume appeared to be in equilibrium with that in other body compartments before but not after acclimatization. Acclimatization altered the rate of protein transfer (and water movement) such that hemodilution was accomplished more rapidly than before acclimatization. Early hemodilution was quite labile and depended upon subject hydration during the first hour of heat exposure.


Chest wall mechanics during artificial ventilation. Chest wall mechanics were studied in six healthy volunteers before and during anesthesia prior to surgery. The intratracheal, esophageal, and intragastric pressures were measured concurrently. Gas flow was measured by pneumotachography and gas volume was obtained from it by electrical integration. Rib cage and abdomen movements were registered with magnetometers, these being calibrated by "isovolume" maneuvers. During spontaneous breathing in the conscious state, rib cage volume displacement corresponded to 40% of the tidal volume. During anesthesia and artificial ventilation, this rose to 72% of the tidal volume. The relative contributions of rib cage and abdomen displacements were not influenced by a change in tidal volume. Compliance was higher with a larger tidal volume, a finding which could be due to a curved pressure-volume relationship of the overall chest wall.


Lung oxygen consumption and mitochondria of alveolar epithelial and endothelial cells. We examined oxygen consumption by lung slices and measured the volume density of mitochondria of granular pneumocytes, alveolar type I cells, and alveolar capillary endothelial cells in several species. We found that lung oxygen consumption (mu-1 02 times h-1 times mg DNA-1) varies inversely with the log of animal body weight and with the species alveolar diameter and directly with the species respiratory rate. The volume density of granular pneumocyte mitochondria show a direct linear correlation with the lung's oxygen consumption and the species respiratory rate, and an inverse linear correlation with the species alveolar diameter. The volume density of mitochondria in type I alveolar epithelial cells and capillary endothelial cells, considered together, did not differ in the two species studied (mouse and rat). We conclude that there are interspecies differences in oxygen consumption by lung cells and that granular pneumocytes contribute to these differences. We suggest that, at least part of these differences, are related to interspecies differences in surfactant secretory activity.


Effect of ambient temperature on heat production and heat loss in burn patients. Four controls and eight burned patients with thermal injury ranging from 7 to 84% total body surface were studied in an environmental chamber at 25 and 33 degrees C ambient temperature and a constant vapor pressure during two consecutive 24-h periods. Hypermetabolism was present in the burn patients in both ambient temperatures and core and skin temperatures were consistently higher than in the normal men despite increased evaporative water loss. The higher environmental temperature decreased metabolic rate in patients with large thermal injuries in whom the decrement in dry heat loss produced by higher ambient temperature exceeded the increase of wet heat loss. In patients with burns smaller than 60%, these changes equaled one another and higher environmental temperature exerted no effect on metabolic rate. Core-skin heat conductivity increased with burn size; patients with large burns were characterized by inadequate core-skin insulation when exposed to the cooler environment, necessitating the compensatory increase of metabolic rate. This increase, however, was small and of the order of 5-8 kcal times m-2 times h-1.


Effect of chronic hypobaria on isolated tracheal preparation. Isolated tracheal preparation (ITP) has been studied from rabbits adapted to 24 days simulated hypobaria (PB = 395 mmHg), corresponding to an elevation of 17,000ft (5,000m). During this daily hypobaric exposure, the growth of these animals was continuous and final hematocrit reached 70%. After 24 days of hypobaric exposure, the sensitivity of ITP was tested to acute hypercapnia and acute anoxia. Acute hypercapnia was induced by aerating a muscle chamber with a gas mixture of 85% oxygen and 15% carbon dioxide. During that time, the PCO2 of the experimental solution increased from 24 to 66 mmHg with a corresponding change of pH from 7.39 to 7.10. ITP from rabbits exposed to chronic hypoxia reveals a greater sensitivity to acute hypercapnia as measured by active tension (AT max) and rate of tension development (dT/dt). Acute anoxia was induced by aerating a muscle chamber with a gas mixture of 95% nitrogen and 5% carbon dioxide. During 20 min of these conditions, the Po2 decreased from 520 to 25 mmHg. Although the contractility diminished at approximately equal rates in both groups in response to acute anoxia, preparation from animals exposed to hypobaria showed statistically a significantly greater ability to recover from the anoxic state.


Effects of airway versus arterial CO2 changes on lung mechanics in dogs. The effects of changes in airway CO2 partial pressure (PAco2) and arterial CO2 partial pressure (Paco2) on lung mechanics were studied in dogs by utilizing unilateral pulmonary artery occlusion and a tracheal divider which allowed separate variation of PAco2 and Paco2. When Paco2 was held at a reasonably normal level, lower than normal PAco2 levels resulted in large compliance decreases, alteration of the complete static pressure-volume curves, and increases in resistance. Invreases in PAco2 to hypercapnic levels did not produce changes. When PAco2 was held at a reasonably normal level, changes in Paco2 levels were positively and directly related to resistance with small and inconsistent effects on compliance and on complete static pressure-volume curves. A combination of low PAco2 and high Paco2 produced large increases in resistance, alterations of the static pressure-volume curve, and decreases in compliance. Vagotomy during the combined stimulus resulted in only a decrease in resistance without change in lung elastic properties. The results suggest that the mechanical effects of airway hypocapnia and systemic hypercapnia are additive. However, small airways effects of low PAco2 appear to be maximal and uninfluenced by the vagally mediated response to Paco2 increases.


Interrelations between pulmonary liquid volumes and lung compliance. We have investigated the relative effects of lung edema and of increases in pulmonary blood volume (PBV) on lung compliance (CL), and also the effects of selective elevations of pulmonary arterial (Ppa) and left atrial (Pla) pressures on PBV and on CL, using an isolated, perfused, and ventilated rabbit lung preparation. Lung weight was continuously recorded. A step rise in Pla at constant flow caused a rapid rise in PBV accompanied by an immediate fall in CL. With maintained high vascular pressures interstitial edema accumulated with no further fall in CL. Not until 3 times the normal amount of extra-vascular fluid had accumulated did a further, secondary reduction in CL occur. When Ppa was elevated to the same level by 1) a rise in flow and 2) a rise in Pla, the latter type of experiment gave 3-5 times larger increases in PBV. Pla elevations with or without rise in Ppa (flow adjusted) gave almost the same rises in PBV. The fall in CL was related to rises in PBV regardless of how such rises were obtained. Our conclusion is that increases in PBV, but not accumulation of interstitial edema, reduced CL in this preparation.


Abnormal tubular permeability in hypothermic perfused kidneys. Isolated canine kidneys perfused with cryoprecipitated plasma at 15 degrees C exhibit unexpectedly low inulin clearance (CIn) and creatinine clearance (CCr) rates. CIn and CCr, as well as p-aminohoppurate (PAH) clearance, varied linearly with urine flow rate, whether the variations in urine flow were spontaneous or induced, either by elevating perfusion pressure or by adding mannitol to the perfusate. Retrograde intraureteral injection (RII) of an isotonic fluid containing dextran, inulin, and PAH, followed by a period of ureteral occlusion and subsequent serial recollection of the injected fluid, revealed that inulin and PAH, relative to dextran, were lost from distal tubular fluid. Similar experiments in anesthetized dogs indicated no loss of inulin or PAH from tubules of in situ kidneys. Renal venous perfusate, collected from isolated kidneys during the low pressure phase of the RII, contained the following percentages of the quantities injected intraluminally: dextran, 9.22%; inulin, 11.0%; and PAH, 22.0%. These data indicate that a low measured glomerular filtration rate in hypothermic perfused kidneys is partly due to diffusion of inulin or creatinine out of the tubular lumen.


Thermoregulatory, metabolic, and cardiovascular response of rats to microwaves. This study was undertaken to determine the effects of 2,450-MHz microwave irradiation on thermoregulation, metabolism, and cardiovascular function of rats. Young adult male animals (430 g) were exposed for 30 min to 2,450-MHz microwaves in a cavity at absorbed dose rates of 0, 4.5, 6.5, or 11.1 mW/G. For animals of the size used in this study, these dose rates represent absorption of energy at the rate of 27.7, 40.1, and 68.2 cal/min, respectively. For a period of 5 h following exposure, measurements were made of colonic temperature, skin temperature, oxygen consumption, carbon dioxide production, respiratory quotient, and heart rate. Rats that received 27.7 cal/min for 30 min exhibited an initial transient increase in colonic and skin temperatures but no alterations in other functions. The group irradiated at 40.1 cal/min had greater elevations in colonic and skin temperatures immediately after exposure, followed by overcompensation and lower than normal colonic temperatures for about 3 h. The metabolic rate was depressed in this group for 3 h. Bradycardia developed within 20 min after exposure and persisted for about 3 h. The group of rats that received 68.2 cal/min for 30 min had responses similar to those of the 40.1 cal/min group, but the changes were more severe and lasted longer. In addition, a number of transient abnormalities were noted in the ECG tracings of rats that had received the highest dose, including irregular rhythms and incomplete heart block. The physiological changes observed in this study can be attributed to the heating induced by irradiation.


Hormonal and electrolyte response to exposure to 17,500 ft. Hormone, electrolyte, and body fluid compartment changes were studied in subjects who either spent time at 10,000 ft before flying to 17,500 ft or were premedicated with acetazolamide and flown directly to 17,500 ft. In the former group, at 10,000 ft, renin and aldosterone were not different from control. Cortisol increased significantly from 9.8 to 19.5 mug/100 ml on the third day. At 17,500 ft, renin, aldosterone and cortisol were significantly elevated on day 3 but had returned to control levels by day 5. Sodium and potassium excretion was significantly reduced at both altitudes. Total body water, extracellular and plasma volume were reduced (P less than 0.05) at 17,500 ft. Subjects pretreated with acetazolamide and flown directly to 17,500 ft had significant increases (P less than 0.001) in plasma renin, aldosterone, and cortisol levels during the first 4 days at altitude. On day 1 there was a decrease of 45% in sodium and 38% in potassium excretion. On day 4 there was a decrease of 63% and 51%, respectively. These changes are not associated with the premedication. The initial changes may reflect the immediate response to stress and alkalosis followed by a return to control levels as the body adapts to altitude.


Blood flow during 2-Torr exposures at different decompression rates. Central and peripheral blood flow of denitrogenated dogs, measured in the femoral artery and aorta, declined rapidly and ceased within mean times of 28, 35, 70, or 90 s after 1-, 10-, 30-, or 60-s decompressions from 258 Torr to 2 Torr, respectively. Neither arterial nor venous hypoxemia was seen after 1-s decompressions since the hypoxic blood did not reach the aorta. In contrast, arterial and venous O2 saturation levels dropped as low as 12 or 6% following 10- to 60-s decompressions since circulation continued. A severe and transient decerebratelike rigidity and subsequent temporary flaccid paralysis of the hind legs was seen during recovery from decompressions slower than 1 s, whereas only a mild temporary flaccid paralysis was frequently present after 1-s decompression. The more severe responses following 10- to 60-s decompressions are associated with the greater hypoxemia after slow decompressions, indicating tissue hypoxia is more severe when decompression rate is slow.


Pulmonary diffusing capacity and capillary blood volume in aging dogs. Single-breath carbon monoxide diffusing capacity (DLco), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) were measured in 24 beagle dogs aged 289-3,882 days. DLco and Vc were a function of age and alveolar volume (Va). Vc decreased with age resulting in changes in DLco. Changes in Vc may have been due to pulmonary morphological changes or to an exaggerated decrease in pulmonary blood flow in old dogs in response to 20-30 cmH-2O transpulmonary pressure. There was no age-related change in Dm.


Static pulmonary compliance in ponies.

Static pulmonary compliance in ponies. Static pulmonary and total compliance during expiration was measured in fifteen healthy anesthetized ponies. Mean body weight of the ponies was 140.6 kg and ranged from 83.6 to 211.4 kg. For the fifteen ponies, mean values and SD were: total compliance (Ct), 168.7 plus or minus 47.2 ml/CMH2O, and mean pulmonary compliance (Cl), 368.4 plus or minus 90.3 ml/cmH2O. Both Ct and Cl were significantly dependent on body weight, calculated surface area, height at the withers, and circumference about the chest. Repeatability of compliance measurement from day to day was confirmed by measuring compliance on consecutive days in four ponies.


Effects of lung inflation on pulmonary arterial blood volume in intact dogs. The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at  a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.


Lung mechanics in hypervolemic pulmonary edema. Extravascular thermal volume of the lung (ETVL) is a double indicator dilution technique of use in measuring pulmonary edema. ETVL and lung mechanics measurements were followed to find a less invasive monitor of pulmonary edema than the double indicator dilution technique. Pulmonary edema was induced by overloading the dogs' circulation with dextran. Phases of overload were defined on the basis of a previous electron microscopic study (Noble et al., Can. Anesthetists Soc. J. 21:275, 1974) of lung biopsies relating anatomic changes to physiologic measurements of ETVL and central blood volume (CBV). Congestion occurred when CBV was elevated and ETVL was not, interstitial edema when ETVL was elevated but smaller than 60% above control and alveolar edema when ETVL greater than 85% above control. Once the dogs were in alveolar edema, they were mechanically ventilated with 4, 8, 12, and 16 cmH2O end-tidal pressure (CPPV). Mean functional residual capacity (FRC) for all 15 dogs did not change up to the time CPPV was applied. Pulmonary resistance did not rise until alveolar edema was present. Once in pulmonary edema, lung compliance always fell as lung water increased. In individual dogs, the compliance fall was directly proportional to the rising lung water. However, the variations in slope and beginning point among dogs made it difficult to predict the amount of lung water from dynamic compliance values. PaO2 fell markedly in alveolar edema as a result of a widened A-a gradient. CPPV did not decrease lung water but did increase FRC and PaO2.


Circulation in rats with Guérin carcinoma. After implantation of Guérin carcinoma in rats, cardiac output (by Evans-blue dilution), distribution of the organ fractions of cardiac output (by Sapirsteins's isotope indicator fractionation technique), nutritive blood flow and circulatory resistance of the organs (including the tumor) were studied. The following parameters were altered proportionately to the weight of the tumor (0.39-84.0 g): a) weight of gut and carcass diminished; b) cardiac index increased, blood pressure and total peripheral resistance decreased; c) tumor fraction of cardiac output was augmented; d) blood flow of the organs increased and their circulatory resistance decreased. Hematocrit decreased from 47.2 to 31.0% 20 days after tumor implantation. In rats with tumor the changes of blood flow may be conditioned by both anemia and the decrease in organ weight.


Total work rate of breathing optimization in CO-2 inhalation and exercise. The hypothesis that respiratory frequency and the relative durations of inspiration and expiration are regulated according to a total cycle work rate minimization criterion was explored. Effects of negative work performed by the respiratory muscles and dead space variation as a function of tidal volume were included in a formulation which yielded a theoretically predictable optimal frequency and relative duration of inspiration and expiration at all levels of ventilation. Predicted cycle characteristics based on measured mechanical parameters were compared with data taken during CO-2 inhalation (3 and 5%) and moderate exercise (MRR = 3 and 6) in three normal human subjects. No major difference in breathing pattern was observed between CO-2 inhalation and exercise. Results suggest that conditions for minimization of total cycle work rate are achieved asympototically as the level of ventilation rises above the resting level. At rest and at low levels of hyperpnea complete work rate optimization is not achieved.


Measurement of axial diffusivities in a model of the bronchial airways. Values for the effective axial diffusivity D for laminar flow of a gas species in the bronchial airways have been obtained as a function of the mean axial gas velocity u by experiment measurements of benzene vapor dispersion in a five generation glass tube model of the bronchial tree. For both inspiration and expiration D is seen to be approximately a linear function of u over the range of Reynolds' numbers 30-2,000 corresponding to peak flows in bronchial generations 0-13 under resting breathing conditions. The diffusivity for expiration is seen to be approximately one-third that for inspiration due presumably to increased radial mixing at bifurcations during expiration. The effective diffusivities relative to the molecular diffusivity can be expressed by the formulas D/Dmol = 1 + 1.08 NPe for inspiration and D/Dmol = 1 + .37 N-Pe for expiration. These velocity dependent diffusivities help to explain the short transit times of gas boluses from mouth to alveoli and will aid in the analysis of airway gas mixing by mathematical transport equations.


Prediction of survival time of rats in severe heat. The response pattern of the rectal temperature of unanesthetized rats exposed to an acute heat in a room of 42.5 degrees C, rh 40% was analyzed in relation to survival time (S), equilibrium rectal temperature (Te), rise in Te from the initial temperature (Delta Te), and the slope of the changes in rectal temperature during the equilibrium period (Gt). A very wide fluctuation of the survival time (from 46.8 to 250.0 min) was observed between individual rats. For prediction of the survival time, following formula was obtained: log(S) = K1 - K2 times log (Te) - K3 times log (Delta  Te) + k4 times 10- minus Gt. K1-4 are constants which differ according to sex. The predicted survival time showed highly constant results in individual rats when measured by repeated exposures. The predicted time coincided well with the survival time actually measured, the difference between the two (measured minus predicted) being 2.2 plus or minus 21.7 min (mean plus or minus SD) IN 77 RATS. There was also a significant correlation between the survival time predicted for acute heat exposure and the actual survival time of individual rats when they were exposed to a chronic heat by daily elevation of the rearing room temperature by 1.0 degrees C.


Continuous in vivo measurement of arterial PO2 in humans. A system suitable for prolonged continuous in vivo measurement of human arterial PO2 is described. The system uses a polarographic electrode developed by Kimmich and Kreuzer, inserted in a specially made shunt between the radial artery and an antecubital vein. Nhe electrode surface is maintained in a fixed position parallel to the flow of blood; blood velocity dependency is small owing to the high flow rate achieved (more than 40 cm/s); clotting is prevented by the material used and the continuous instillation of heparin through the arterial end of the shunt. The system has been tested in vitro; it is stable (variation less than 0.5% in 24 h), linear and precise (plus or minus 0.2%) in a broad range of PO2 values (from about 10 mmHg to more than 700 mmHg); its response time is 0.4 s per 95% of deflection. It has been applied to 35 patients for periods ranging between 6 and 24 h; most of the patients were ventilated by an Engstrom respirator.


Validation of continuous determination of respired gases during steady-state exercise. A continuous-flow sampling system (CFS) for convenient and rapid determination of respiratory gas exchange during steady-state exercise was described. CFS was compared to the classical bag collection system (BCS) by utilizing both methods concurrently during exercise for analysis of 32 1-min gas samples. The gas collected by BCS was analyzed by chemical absorption. The error in the gas mixing and sampling technique of CFS contributed to the absolute error of the gas analysis but did not adversely affect the reliability. The linear regression analysis on the data suggests that CFS is a relatively accurate and reliable system for use at light and moderate levels of steady-state work. However, it is hypothesized that unsteady-state conditions and heavy exercise, which elicits high ventilation rates, would compromise the accuracy and reliability of CFS. Therefore, it is recommended that the traditional BCS be utilized for determination of maximal oxygen uptake.


Electronic particle size measurements of platelet aggregates formed in vitro. The aggregation of human platelets induced by adenosine diphosphate (ADP) was used to evaluate electronic particle size analyzer measurements of platelet aggregates in plasma. As platelets began to clump in plasma, the total volume and the diameter of individual aggregates increased; after a time dependent on experimental conditions, the diameter increased but the total volume remained unchanged. Similar but opposite changes in size distribution occurred during platelet deaggregation. The total volume of aggregates formed in plasma varied (linear correlation coefficient = 0.99) with the total volume of platelets which were available to clump and with simultaneous changes in optical density. The diameter of the aggregates varied with the concentration of, and time of exposure to, ADP and with the total volume of platelets and aggregates in plasma was not different from that of control platelets in untreated plasma, the individual platelets aggregated without an accompanying increase in size. This study demonstrates that platelet aggregation can be characterized by electronic measurements of the size distribution of platelet aggregates.


Prediction of body density in young and middle-aged women. The purpose of this investigation was to predict body density of young and middle-aged women and to determine if the use of a greater variety of variables, particularly those for fat in the bust and hip regions, increases the predictability of body density. Body density determined by the hydrostatic technique (dependent variable) was obtained from 83 volunteer young women and 60 middle-aged women ranging from 18 to 22 and 33 to 50 yr of age, respectively. Independent variables included 8 skinfold, 13 girth, and 7 diameter measures; age; height; weight; and bra and cup sizes. Mean body density for young women was 1.043 g/ml (SD plus or minus 0.014) and percent fat, 24.8 (SD plus or minus 6.4); 1.031 g/ml (SD plus or minus 0.015) and 29.8% (SD plus or minus 6.7) for middle aged subjects. Percent fat was calculated by the formula of Siri. Factor analysis was used to examine the dimensions measured by the independent variables as a function of age. A multiple regression model was used to develop predictions of body density from the independent variables. The best combination of four variables for predicting body density was skinfold thigh, skinfold suprailiac, cup size, skinfold suprailiac, girth waist, and skinfold thigh (R = 0.89) for middle-aged women. The data showed that the highest predictons were found by using combinations of skinfold, girth, and diameter variables; cup size also supported the need for different regression equations for different age groups.


Chronic cannulation for intermittent intravenous fluid administration. A system is described for rapid and effective venous cannulation for long-term administration of fluids in rabbits. This method is completely free of any harness or sling-type apparatus and in no way interferes with the normal mobility of the animal. The animals maintained in this way have participated in programs of tri-weekly administration (2-3 ml/dose) of fluid for as long as 5 mo.